| Hugh Laurie | Dr. Gregory House |
| Lisa Edelstein | Dr. Lisa Cuddy |
| Omar Epps | Dr. Eric Foreman |
| Robert Sean Leonard | Dr. James Wilson |
| Jesse Spencer | Dr. Robert Chase |
| Peter Jacobson | Dr. Chris Taub |
| Olivia Wilde | Thirteen |
| China Shavers | Hanna
(as China Jesusita Shavers) |
| Doug Kruse | Jay Dolce |
| Jamie McShane | Cpt. McCreaney |
| Desean Terry | Charles |
| Angel Oquendo | EMT Coumont |
| Kimberly M. Bailey | Dolce's Wife |
| Jason Paul Field | Rescue Worker #1 |
| Edward Chen | Rescue Worker #2
(as Teddy Chen Culver) |
| Matthew Brent | Dislocated Shoulder |
| Caroline Pho | Head Wound |
| Marty Hrejsa | Purple Toes |
| Bobbin Bergstrom | Nurse |
| Christopher Baskerville | Hospital Patient |
| Ward Edmondson | Public Safety Officer
(uncredited) |
| Joshua Enbom | Firefighter
(uncredited) |
| Waymond Lee | Injured Wreckage Survivor
(uncredited) |
| Joseph O'Brien | Restaurant Patron
(uncredited) |
| David Pryor | Search and Rescue Team
(uncredited) |
| Leonard Jonathan Ruebe | Fire Fighter
(uncredited) |
| Alen Toric | Firefighter
(uncredited) |